Malaria

What is Malaria Malaria is fatal disease caused by a

parasite that commonly infects a certain type of mosquito which feeds on humans

Four kinds of malaria parasites have long been known to infect humans: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae (P. knowlesi, a type of malaria causing malaria that is transmitted from animal to human ("zoonotic" malaria).

Although malaria can be a deadly disease, illness and death from malaria can usually be prevented.

How is malaria transmitted? Usually, people get malaria by being bitten by

an infective female Anopheles mosquito. Only Anopheles mosquitoes can transmit

malaria and they must have been infected through a previous blood meal taken from an infected person.

Because the malaria parasite is found in red blood cells of an infected person, malaria can also be transmitted through :

- blood transfusion, - organ transplant, or - the shared use of needles or syringes contaminated with blood. - Malaria may also be transmitted from a mother to her unborn infant before or during delivery ("congenital" malaria).

Malaria Parasites Malaria parasites are micro-organisms that

belong to the genus Plasmodium. There are more than 100 species of Plasmodium,

which can infect many animal species such as reptiles, birds, and various mammals.

Four species of Plasmodium have long been recognized to infect humans in nature Plasmodium falciparum, P. vivax, P. ovale, and P. malariae (P. knowlesi, a type of malaria causing malaria that is transmitted from animal to human ("zoonotic" malaria).

Plasmodium falciparum which is found worldwide in tropical and

subtropical areas. P. falciparum can cause severe malaria

(severe anemia,cerebralmalaria and black water fever ).

36 – 48 hours cycle ( malaria tertiana maligna )

Infected all stage of RBC parasitemia level 50 %

Maurer’s dots ( single blue dots bigger than Schoefner dots)

Cresent gametocyt Trofozoit ring form,multiple ring form Skizon is rarely seen in blood stream, mature

skizon contained 18 – 24 merozoites

Plasmodium falciparum

Plasmodium vivax which is found mostly in Asia, Latin America, and in some

parts of Africa. P. vivax (as well as P. ovale) has dormant liver stages

("hypnozoites") ("relapse“). Enlargement of erythrocyte 48 hours cycle ( malaria tertiana benigna ) Parasitemia 2 – 5 % Schuffner dots Trophozoites are ameboid Mature skizon contains 12 – 24 merozoites Infected reticulocytes All development stadiums are found in blood stream

Plasmodium vivax

Plasmodium ovale P. ovale is found mostly in Africa (especially

West Africa) and the islands of the western Pacific.

It is biologically and morphologically very similar to P. vivax

Hipnozoite form relaps but rare than P.vivax 48 hours cycle ( malaria tertiana) Infected reticulocytes parasitemia level 2 – 5

% The shape of infected RBC oval shape and

bigger The ring form < P.vivax Trophozoites less amoeboid Mature skizon contains 8 merozoites

Plasmodium ovale

Plasmodium malariae found worldwide, is the only human malaria

parasite species that has a quartan cycle (three-day cycle). In some chronically infected patients P. malariae can cause serious complications such as the nephrotic syndrome.

Incubation period longer than P.vivax and P ovale periode ( 27 – 40 days)

Infected old RBC No enlargement of RBC No dots Mature skizons contain – 12 merozoites

(rossette) Trofozoites band form

Plasmodium malariae

Plasmodium knowlesi is found throughout

Southeast Asia as a natural pathogen of long-tailed and pig-tailed macaques. 

It has recently been shown to be a significant cause of zoonotic malaria in that region, particularly in Malaysia. 

P. knowlesi has a 24-hour replication cycle and so can rapidly progress from an uncomplicated to a severe infection; fatal cases have been reported.

Anopheles mosquitoes Malaria is transmitted among humans by female

mosquitoes of the genus Anopheles. There are approximately 3,500 species of mosquitoes grouped into 41 genera, only 30-40 species transmit malaria (i.e., are "vectors") in nature.

Female mosquitoes take blood meals to carry out egg production, and such blood meals are the link between the human and the mosquito hosts in the parasite life cycle.

The successful development of the malaria parasite in the mosquito (from the "gametocyte" stage to the "sporozoite" stage) depends on several factors.

The most important is ambient temperature and humidity (higher temperatures accelerate the parasite growth in the mosquito) and whether the Anopheles survives long enough to allow the parasite to complete its cycle in the mosquito host ("sporogonic" or "extrinsic" cycle, duration 10 to 18 days).

Differently from the human host, the mosquito host does not suffer noticeably from the presence of the parasites.

Life Cycle in Human The natural ecology of malaria involves malaria

parasites infecting successively two types of hosts: humans and female Anopheles mosquitoes.

In humans, the parasites grow and multiply first in the liver cells and then in the red cells of the blood.

In the blood, successive broods of parasites grow inside the red cells and destroy them, releasing daughter parasites ("merozoites") that continue the cycle by invading other red cells.

The blood stage parasites are those that cause the symptoms of malaria.

When certain forms of blood stage parasites ("gametocytes") are picked up by a female Anopheles mosquito during a blood meal, they start another, different cycle of growth and multiplication in the mosquito.

Life Cycle in Mosquito After 10-18 days, the parasites are found (as

"sporozoites") in the mosquito's salivary glands. When the Anopheles mosquito takes a blood meal

on another human, the sporozoites are injected with the mosquito's saliva and start another human infection when they parasitize the liver cells.

Thus the mosquito carries the disease from one human to another (acting as a "vector").

Differently from the human host, the mosquito vector does not suffer from the presence of the parasites.

The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host .

Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.)

After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ).

Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites .

Some parasites differentiate into sexual erythrocytic stages (gametocytes) . Blood stage parasites are responsible for the clinical manifestations of the disease.

The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal .

The parasites’ multiplication in the mosquito is known as the sporogonic cycle .

While in the mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes .

The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts .

The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.

Pathogenesis Infection with malaria parasites may result in a

wide variety of symptoms, ranging from absent or very mild symptoms to severe disease and even death. Malaria disease can be categorized as uncomplicated or severe (complicated).

In general, malaria is a curable disease if diagnosed and treated promptly and correctly.

All the clinical symptoms associated with malaria are caused by the asexual erythrocytic or blood stage parasites.

Pathogenesis When the parasite develops in the erythrocyte,

numerous known and unknown waste substances such as hemozoin pigment and other toxic factors accumulate in the infected red blood cell.

These are dumped into the bloodstream when the infected cells lyse and release invasive merozoites.

The hemozoin and other toxic factors such as glucose phosphate isomerase (GPI) stimulate macrophages and other cells to produce cytokines and other soluble factors which act to produce fever and rigors and probably influence other severe pathophysiology associated with malaria.

Incubation Periode The incubation period in most cases varies from 7 to 30

days. The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.

Antimalarial drugs taken for prophylaxis by travelers can delay the appearance of malaria symptoms by weeks or months, long after the traveler has left the malaria-endemic area.

Returned travelers should always remind their health-care providers of any travel in areas where malaria occurs during the past 12 months.

In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites ("hypnozoites") that may reactivate.

Uncomplicated Malaria The classical (but rarely observed) malaria attack lasts

6-10 hours. It consists of1. a cold stage (sensation of cold, shivering) 2. a hot stage (fever, headaches, vomiting; seizures in young children) 3. and finally a sweating stage (sweats, return to normal temperature, tiredness).

Classically (but infrequently observed) the attacks occur every second day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan" parasite (P. malariae).

More commonly, the patient presents with a combination of the following symptoms:Fever , Chills , Sweats , Headaches , Nausea and vomiting Body aches , and General malaise

Severe Malaria Cerebral malaria, with abnormal behavior, impairment of

consciousness, seizures, coma, or other neurologic abnormalities

Severe anemia due to hemolysis (destruction of the red blood cells)

Hemoglobinuria (hemoglobin in the urine) due to hemolysis Acute respiratory distress syndrome (ARDS), an inflammatory

reaction in the lungs that inhibits oxygen exchange, which may occur even after the parasite counts have decreased in response to treatment

Abnormalities in blood coagulation Low blood pressure caused by cardiovascular collapse Acute kidney failure Hyperparasitemia, where more than 5% of the red blood cells

are infected by malaria parasites Metabolic acidosis (excessive acidity in the blood and tissue

fluids), often in association with hypoglycemia Hypoglycemia (low blood glucose). Hypoglycemia may also

occur in pregnant women with uncomplicated malaria, or after treatment with quinine.

Diagnosis Microscopic Diagnosis

Malaria parasites can be identified by examining under the microscope a drop of the patient's blood, spread out as a "blood smear" on a microscope slide. Prior to examination, the specimen is stained (most often with the Giemsa stain) to give the parasites a distinctive appearance. This technique remains the gold standard for laboratory confirmation of malaria. However, it depends on the quality of the reagents, of the microscope, and on the experience of the laboratorian.

Antigen Detection Molecular Diagnosis Serology Drug Resistance Tests

TreatmentTreatment a patient with malaria

depends on: The type (species) of the infecting parasite The area where the infection was acquired

and its drug-resistance status The clinical status of the patient Any accompanying illness or condition Pregnancy Drug allergies, or other medications taken

by the patient

Treatment Artemisinin (Artemisinin Combination

Therapy/ ACT) sebagai terapi lini pertama dalam penanganan malaria tanpa komplikasi di daerah yang telah dikonfirmasi multidrug resistance untuk mencegah kegagalan terapi, resistensi dan relaps.

Penggunaan ACT merupakan kombinasi dari dua atau lebih obat anti malaria

Saat ini terdapat dua regimen ACT yang digunakan dalam program malaria yaitu artesunat amodiakuin (AAQ) dan dihidroartemisinin pip erakuin (DHP). 

Prevention Keeping mosquitoes from biting you,

especially at night Taking antimalarial drugs to kill the parasites Spraying insecticides on your home's walls to

kill adult mosquitoes that come inside Sleeping under bed nets—especially effective

if they have been treated with insecticide, and Using insect repellent and wearing long-

sleeved clothing if out of doors at night. Any traveler who becomes ill with a fever or

flu-like illness while traveling, and up to 1 year after returning home, should immediately seek professional medical care.

P. FALCIPARUMParasit ini menyerang eritrosit tua dan

mudaManifestasi klinis : hiperparasitemia,

anemia, malaria serebral, ikterus, splenomegali, gagal ginjal dan koma

Siklus : 36- 48jam

Trofozoit Ciri morfologisInti berwarna merah,

protoplasma bentuk cincin atau seperti garis biru pada tepi eritrosit,

SDM tidak membesarBentuk cincin halus

dan kecilSering ada double dots

( 2 inti)

P.Falciparum

Makrogametosit (betina) Ciri morfologisBentuk khas seperti

pisang (banana form), tampak pigmen coklat tua di sekitar inti

Makrogametosit berbentuk pisang langsing, inti padat, dikelilingi pigmen, sitoplasma berwarna biru:

Morfologi

Mikrogametosit(jantan) Ciri morfologis

Mikrogametosit berbentuk pisang, agak gemuk,

ujungmya tumpul, inti dikelilingi pigmen, sitoplasma berwarna

merah pucat.

Morfologi

PLASMODIUM VIVAXCenderung menginfeksi sel eritrosit yang mudaSel eritrosit yang terinfeksi berukuran lebih besar

daripada eritrosit normalSiklus 48 jamTerdapat titik Schuffner setelah 8 – 10 jamGejala klinis : demam, menggigil, anemia,

splenomegaliPerjalanan penyakit relaps ( stadium hipnozoit

didalam hepar )

Trofozoit Ciri morfologis

Cincin berukuran 1/3 sel

bentuknya tidak teratur ( amoeboid )

Tampak Vakoula, inti lebih besar

Morfologi P.vivax

schizon Ciri morfologis

Protoplasma padat ( inti sudah terbagi ) menjadi merozoit

Merozoit berjumlah 12-24 buah

Morfologi

Gametosit Ciri morfologis

Mengisi seluruh eritrosit,

Sitoplasma homogen

Pigmen halus dan difus

Morfologi

PLASMODIUM OVALECenderung menginfeksi sel eritrosit yang

mudaSel eritrosit yang terinfeksi berukuran lebih

besar daripada eritrosit normal dan berumbai (oval)

Siklus 48 jamTerdapat titik Schuffner pada fase awal

infeksiPerjalanan penyakit relaps ( stadium

hipnozoit didalam hepar ) namun jarangGejala klinis lebih ringan dari P.vivax

Trofozoit Ciri morfologis

Satu kromatin dot, berbentuk cincin, inti padat

Trofosoit dewasa mempunyai pigmen kasar

SDM berbentuk oval dan berfimbriae

Morfologi P.ovale

schizon Ciri morfologis

Lebih kecil dari P.vivax

Jumlah merozoit biasanya 8 buah

Masa kromatin sedikit, pigmen kasar

Morfologi

gametosit Ciri morfologisBentuk oval dengan

tepi berumbaiSitoplasma

homogenPigmen difus

berwarna coklat meliputi parasit

Morfologi

PLASMODIUM MALARIAECenderung menginfeksi sel eritrosit

yang tuaSel eritrosit yang terinfeksi berukuran

normalSiklus 72 jamTidak terdapat titik – titik yang khas

Trofozoit Ciri morfologis

Berbentuk cincin dan pita atau band form

Pigmen kasar dan berwarna coklat tua

Morfologi

schizon Ciri morfologis

Plasma dalam inti sudah terbagi

Merozoit berjumlah 8-12 buah

Pigmen-pigmen kasar berkumpul di tengah dikelilingi oleh merozoit yang letaknya teratur disebut “rosette”

Morfologi

gametosit Ciri morfologis

Sitoplasma menjadi homogen

dikelilingi pigmen kasar berwarna coklat

Morfologi